On March 15, 2022 BostonGene Corporation and Thomas Jefferson University reported the online publication of the manuscript, "Tadalafil enhances immune response to neoadjuvant nivolumab in resectable head and neck squamous cell carcinoma" in the American Association for Cancer Research (AACR) (Free AACR Whitepaper) journal Clinical Cancer Research (Press release, BostonGene, MAR 15, 2022, View Source [SID1234610132]). The study revealed pretreatment head and neck squamous cell carcinoma specimens contain distinct HPV status-dependent signatures predictive of immunotherapy response, while post-treatment specimens treated with combination nivolumab and tadalafil exhibit tumor immune microenvironments enriched with B and natural killer cell-associated gene signatures.
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The study evaluated the molecular, cellular and immunologic profiles of head and neck cancer patients treated with nivolumab alone versus combined nivolumab and tadalafil. The first arm received nivolumab, a PD-1 inhibitor, intravenously on days 1 and 15 prior to surgery on day 28. The second arm received the same treatment with the addition of daily oral tadalafil, a PDE5 inhibitor, during the 28 days before surgery. Groups were stratified by HPV status. Imaging, blood, and tumor tissue obtained at pre- and post-treatment time points were used for correlative analysis. For the analysis BostonGene applied its integrated whole exome and whole transcriptome workflow to simultaneously assess the tumor and tumor microenvironment profiles. The results show the tumor proliferation rate is a negative predictor of response, while T cells are predictive of a positive response in HPV-negative head and neck cancer patients. The addition of tadalafil to traditional PD-1 inhibitor therapy increases B and natural killer cell signatures present in post treatment biopsies of therapy responders. Overall, the results of the study demonstrates adding tadalafil to nivolumab in head and neck cancers advocates for further trials of PDE-5 inhibition in this context.
Adam J. Luginbuhl, M.D., Associate Professor of Otolaryngology at Thomas Jefferson University, and researcher at the Sidney Kimmel Cancer Center – Jefferson Health, says, "The study provides a comprehensive analysis of patient response to immune checkpoint inhibitors in both HPV-positive and HPV-negative head and neck cancers and can serve as a foundation for further studies on PDE-5 inhibition."
"Collaborating with Thomas Jefferson University underscores our commitment to improving the landscape of therapies for precision cancer medicine," says Nathan Fowler, MD, Chief Medical Officer at BostonGene. "We hope to see additional clinical trials demonstrating that signatures predictive of immunotherapy response benefit head and neck cancer patients in neoadjuvant settings."